WO2016175240A1 - 多汗症治療用外用剤 - Google Patents

多汗症治療用外用剤 Download PDF

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Publication number
WO2016175240A1
WO2016175240A1 PCT/JP2016/063188 JP2016063188W WO2016175240A1 WO 2016175240 A1 WO2016175240 A1 WO 2016175240A1 JP 2016063188 W JP2016063188 W JP 2016063188W WO 2016175240 A1 WO2016175240 A1 WO 2016175240A1
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WO
WIPO (PCT)
Prior art keywords
agent
external preparation
oxybutynin
lotion
anticholinergic
Prior art date
Application number
PCT/JP2016/063188
Other languages
English (en)
French (fr)
Japanese (ja)
Inventor
佳奈 今村
知宏 篠田
真吾 染川
康也 道中
Original Assignee
久光製薬株式会社
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 久光製薬株式会社 filed Critical 久光製薬株式会社
Priority to KR1020177027272A priority Critical patent/KR101937072B1/ko
Priority to JP2017515577A priority patent/JP6387458B2/ja
Priority to EP16786516.1A priority patent/EP3290053B1/en
Priority to CN201680019209.XA priority patent/CN107427582B/zh
Priority to ES16786516T priority patent/ES2861052T3/es
Priority to US15/568,432 priority patent/US10525132B2/en
Publication of WO2016175240A1 publication Critical patent/WO2016175240A1/ja

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present invention relates to an external preparation for treating hyperhidrosis.
  • Patent Documents 1 and 2 As a method for treating hyperhidrosis, a method of administering an external composition containing an anticholinergic agent such as oxybutynin has been proposed (Patent Documents 1 and 2).
  • An anticholinergic agent is a drug that inhibits binding of acetylcholine to a muscarinic acetylcholine receptor and suppresses parasympathetic nerves. Therefore, administration of anticholinergics may cause side effects such as dry mouth.
  • the present inventors In order to treat hyperhidrosis while suppressing the above-mentioned side effects, the present inventors consider that it is important to increase the accumulation of anticholinergic drugs on sweat glands, which are the appendages of the skin, and have conducted intensive studies. It was. As a result, the present inventors have found that a predetermined salt enhances the accumulation of an anticholinergic drug on the appendages of the skin, and have completed the present invention.
  • the present invention provides an external preparation for treating hyperhidrosis comprising water, an anticholinergic agent, and one or more salts selected from the group consisting of lactate, tartrate, acetate and phosphate.
  • the anticholinergic agent may be oxybutynin or a pharmaceutically acceptable salt thereof.
  • the salt may be sodium lactate.
  • the external preparation may be a liquid agent.
  • the solution may be a lotion dosage form.
  • the external preparation for treating hyperhidrosis according to the present invention contains one or more salts selected from the group consisting of lactate, tartrate, acetate and phosphate. Therefore, the accumulation of anticholinergic agents on the skin appendages is high.
  • One embodiment of the present invention is an external preparation for treating hyperhidrosis comprising water, an anticholinergic agent and one or more salts selected from the group consisting of lactate, tartrate, acetate and phosphate. .
  • the anticholinergic agent is not particularly limited as long as it is an arbitrary drug having an anticholinergic effect, for example, oxybutynin, imidafenacin, tropium, tolterodine, glycopyrrolate, propantheline, benztropine, atropine, homatropine, tropicamide, benactidine, Biberidene, scopolamine, butyl scopolamine bromide, cyclopentrate, darifenacin, dexetimide, dicyclomine, emepronium, hexahydrosiladiphenidol, octyronium, orphenadrine, oxyphenonium, pyrenzepine, procyclidine, darotropium, ipratropium, tiotropium, oxytropium, oxitropium Quinidine, trihexyphenidyl, mivacurium, atracurium, doxaclium, cis atracurium, vector Bro
  • the anticholinergic agent is preferably oxybutynin or a pharmaceutically acceptable salt thereof.
  • the pharmaceutically acceptable salt of oxybutynin include oxybutynin hydrochloride.
  • the content of the anticholinergic agent may be, for example, 0.5 to 35% by mass or 0.5 to 15% by mass based on the total mass of the external preparation.
  • the external preparation contains one or more salts selected from the group consisting of lactate, tartrate, acetate and phosphate
  • the salt may be anhydrous or hydrated.
  • Lactic acid may be either L-form or D-form, or any mixture thereof.
  • Tartaric acid may be any of L-form, D-form and meso-form, or any mixture thereof.
  • Salts include, for example, salts with monovalent metals such as sodium, potassium and lithium, salts with divalent metals such as calcium and magnesium, salts with trivalent metals such as aluminum, and ammonia, ethylenediamine, triethylamine, And salts with amine compounds such as diethanolamine, triethanolamine and meglumine.
  • the salt is preferably lactate, and more preferably sodium lactate.
  • the content of the salt may be, for example, 0.1 to 10% by mass based on the total mass of the external preparation.
  • the molar ratio of the anticholinergic agent and the salt in the external preparation may be, for example, in the range of 1: 0.5 to 1: 2.
  • the external preparation for treating hyperhidrosis may be, for example, a liquid, a cream, a gel, or an aqueous ointment.
  • the external preparation for treating hyperhidrosis is a liquid
  • water in the liquid becomes a medium for dissolving or dispersing the anticholinergic agent, the salt, and other components.
  • the water content may be, for example, 10 to 99% by mass based on the total mass of the liquid agent.
  • the liquid preparation includes lower alcohols, surfactants, storage stabilizers, fats and oils, solubilizers, fillers, moisturizers, pH regulators, osmotic pressure regulators, thickeners, cooling agents, astringents and A vasoconstrictor or the like may be included.
  • Lower alcohol enhances the solubility and dispersibility of anticholinergic drugs and enhances the distribution of anticholinergic drugs to the skin.
  • Specific examples of the lower alcohol include methanol, ethanol and isopropanol.
  • the content of the lower alcohol may be, for example, 0 to 90% by mass based on the total mass of the liquid agent.
  • the surfactant is useful for emulsifying the anticholinergic agent in a medium such as water.
  • the surfactant include nonionic surfactants (polysorbate 20, polysorbate 80, polysorbate 60, polyoxyethylene hydrogenated castor oil 20, polyoxyethylene hydrogenated castor oil 40, polyoxyethylene hydrogenated castor oil 60, and the like).
  • ionic surfactants and amphoteric surfactants may be, for example, 0 to 10% by mass based on the total mass of the liquid agent.
  • the storage stabilizer examples include paraben, isopropylmethylphenol, phenoxyethanol and thymol.
  • fats and oils and solubilizers include fatty acids, fatty acid esters and aliphatic alcohols.
  • the filler examples include inorganic powder (such as talc, montmorillonite, smectite and kaolin) and organic powder.
  • humectant examples include polyhydric alcohols, sugars, urea, petrolatum, and paraffin.
  • the pH of the solution can be in the range of 4.5 to 7.5.
  • the measurement of pH is performed using a composite glass electrode in accordance with “2.54 pH measurement method” of the general test method of the 16th revision Japanese Pharmacopoeia.
  • Liquids may be in the form of lotions and liniments and are contained in suitable containers (eg, spray containers for spraying liquids, containers for applying liquids and aerosol containers). It may be in the form of a coating agent or a spray.
  • suitable containers eg, spray containers for spraying liquids, containers for applying liquids and aerosol containers. It may be in the form of a coating agent or a spray.
  • the external preparation for treating hyperhidrosis is a cream
  • water, an anticholinergic agent and the salt may be blended in the cream base.
  • the cream base is not particularly limited, and may be selected from those usually used such as petrolatum or higher alcohol.
  • the cream base may be added with additives usually added to the cream, such as emulsifiers, preservatives, absorption accelerators, and anti-rash agents.
  • a gel-like cream agent can also be obtained by adding a gelling agent and a neutralizing agent to the cream agent and adjusting the pH to 4-8.
  • Such a gel cream has properties intermediate between the cream and the gel.
  • the water content in the cream may be, for example, 0.5 to 70% by weight based on the total weight of the cream.
  • the external preparation for treating hyperhidrosis is a gel
  • water, an anticholinergic agent and the salt may be blended in the gel base.
  • the gel base is not particularly limited, and may be selected from those usually used such as higher alcohols.
  • the gel base may be added with additives usually added to the gel, such as a gelling agent, a neutralizing agent, a surfactant, an absorption accelerator, a solubilizing agent, and an anti-rash agent.
  • the water content in the gel may be, for example, 0.5 to 70% by mass based on the total mass of the gel.
  • water, the anticholinergic agent and the salt may be dissolved or dispersed in a water-soluble base.
  • the water-soluble base is not particularly limited, and may be selected from commonly used ones such as solid polyethylene glycol.
  • additives usually added to an aqueous ointment such as an absorption accelerator, a humectant, and a rash prevention agent, may be added.
  • the water content in the aqueous ointment may be, for example, 0.5 to 30% by mass based on the total mass of the aqueous ointment.
  • the external preparation for treating hyperhidrosis can be produced by mixing and mixing the above components.
  • the external preparation is shaken, if necessary, and the components are mixed homogeneously. Then, the external preparation is applied, sprayed or sprayed on the skin site where sweating is to be suppressed, and spread as necessary.
  • Test example 2 Lotions were prepared according to the composition in Table 3. The antiperspirant action of the lotion was measured by the pilocarpine-induced sweat test. Further, by the same method as in Test Example 1, a lotion was applied to the skin of pigs, and the concentration of oxybutynin was measured.
  • FIGS. FIG. 2 shows the result of the pilocarpine-induced sweat test when the lotion application amount is 10 ⁇ L
  • FIG. 3 shows the result of the pilocarpine-induced sweat test when the lotion application amount is 15 ⁇ L. It was confirmed that the antiperspirant action of the lotion was dependent on the oxybutynin concentration. It was also confirmed that the amount of oxybutynin accumulated in the hair follicle was dependent on the oxybutynin concentration.
  • Test example 3 Lotions were prepared according to the composition in Table 4. The antiperspirant action of the lotion was measured by the pilocarpine-induced sweat test.
  • the results are shown in Table 5.
  • the lotion containing lactate or acetate showed a stronger antiperspirant action than the lotion containing no salt.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Dermatology (AREA)
  • Emergency Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicinal Preparation (AREA)
  • Cosmetics (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
PCT/JP2016/063188 2015-04-30 2016-04-27 多汗症治療用外用剤 WO2016175240A1 (ja)

Priority Applications (6)

Application Number Priority Date Filing Date Title
KR1020177027272A KR101937072B1 (ko) 2015-04-30 2016-04-27 다한증 치료용 외용제
JP2017515577A JP6387458B2 (ja) 2015-04-30 2016-04-27 多汗症治療用外用剤
EP16786516.1A EP3290053B1 (en) 2015-04-30 2016-04-27 Topical composition comprising oxybutynin for the treatment of hyperhidrosis
CN201680019209.XA CN107427582B (zh) 2015-04-30 2016-04-27 多汗症治疗用外用剂
ES16786516T ES2861052T3 (es) 2015-04-30 2016-04-27 Composición tópica que comprende oxibutinina para el tratamiento de la hiperhidrosis
US15/568,432 US10525132B2 (en) 2015-04-30 2016-04-27 External agent for treating hyperhidrosis

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2015-092946 2015-04-30
JP2015092946 2015-04-30

Publications (1)

Publication Number Publication Date
WO2016175240A1 true WO2016175240A1 (ja) 2016-11-03

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PCT/JP2016/063188 WO2016175240A1 (ja) 2015-04-30 2016-04-27 多汗症治療用外用剤

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US (1) US10525132B2 (es)
EP (1) EP3290053B1 (es)
JP (1) JP6387458B2 (es)
KR (1) KR101937072B1 (es)
CN (1) CN107427582B (es)
ES (1) ES2861052T3 (es)
TW (1) TWI713521B (es)
WO (1) WO2016175240A1 (es)

Families Citing this family (4)

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Publication number Priority date Publication date Assignee Title
CN106137955B (zh) * 2016-08-17 2021-10-29 杭州百诚医药科技股份有限公司 一种外用噻托溴铵制剂的止汗用途
NL2023160B1 (en) * 2018-05-17 2020-05-20 Notoxins Ip B V Aqueous formulations comprising oxybutynin for topical treatment of skin diseases
WO2019236429A1 (en) * 2018-06-04 2019-12-12 Nm Therapeutics, Llc Method and apparatus for treatment of hyperhidrosis
EP4140476A1 (en) * 2021-08-25 2023-03-01 Health Innovation Technology Transfer, S.L. An oil-in-water emulsion gel comprising tiotropium bromide

Citations (2)

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Publication number Priority date Publication date Assignee Title
WO1995028914A1 (fr) * 1994-04-21 1995-11-02 Hisamitsu Pharmaceutical Co., Inc. Composition de base administree par voie percutanee et composition medicamenteuse administree par voie percutanee obtenue a partir de cette derniere
WO2010062930A1 (en) * 2008-11-26 2010-06-03 Dry Pharma, Llc Compositions and methods for hyperhidrosis

Family Cites Families (8)

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US7504114B1 (en) 1999-04-13 2009-03-17 Hisamitsu Pharmaceuticals Preparations for percutaneous absorption
US7029694B2 (en) * 2000-04-26 2006-04-18 Watson Laboratories, Inc. Compositions and methods for transdermal oxybutynin therapy
AU2012216593B2 (en) 2002-11-01 2014-09-25 Allergan Sales, Llc Compositions and methods for transdermal oxybutynin therapy
CN101340884A (zh) * 2005-10-19 2009-01-07 曼尼·马纳舍·辛格尔 用于治疗多汗症的方法
KR101317924B1 (ko) 2011-05-17 2013-10-16 김동진 글리코피롤레이트의 합성방법 및 이 활성성분을 함유하는 약학적 조성물의 제조방법
CA2858156C (fr) * 2011-12-23 2018-12-04 Fives Fcb Dispositif de refroidissement d'une embouchure d'un four tubulaire rotatif par soufflage d'air frais
US20140037713A1 (en) 2012-08-03 2014-02-06 Antares Pharma Ipl, Ag Transdermal compositions for anti-cholinergic agents
MX363601B (es) * 2013-03-15 2019-03-28 Bodor Laboratories Inc Ésteres de glicopirrolato anticolinérgico para el tratamiento de hiperhidrosis.

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995028914A1 (fr) * 1994-04-21 1995-11-02 Hisamitsu Pharmaceutical Co., Inc. Composition de base administree par voie percutanee et composition medicamenteuse administree par voie percutanee obtenue a partir de cette derniere
WO2010062930A1 (en) * 2008-11-26 2010-06-03 Dry Pharma, Llc Compositions and methods for hyperhidrosis

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
DEL BOZ, J: "Systemic treatment ot hypernidrosis", ACTAS DERMO-SIFILIOGRAFICAS, vol. 106, no. 4, 6 April 2015 (2015-04-06), pages 271 - 277, XP029220272, ISSN: 0001-7310 *

Also Published As

Publication number Publication date
EP3290053B1 (en) 2021-02-17
TW201703767A (zh) 2017-02-01
CN107427582A (zh) 2017-12-01
JPWO2016175240A1 (ja) 2017-11-16
CN107427582B (zh) 2021-03-05
KR101937072B1 (ko) 2019-01-09
JP6387458B2 (ja) 2018-09-05
ES2861052T3 (es) 2021-10-05
US20180140704A1 (en) 2018-05-24
TWI713521B (zh) 2020-12-21
EP3290053A1 (en) 2018-03-07
EP3290053A4 (en) 2019-01-09
US10525132B2 (en) 2020-01-07
KR20170120168A (ko) 2017-10-30

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